Kalenga, et al., studied a Belgian NDI family which was unusual in the respect that though two of the male siblings had the same V2R genemutation, the older, a 45-year-old, had severe NDI symptoms and the younger, a 33-year-old, had mild ones. (The mother carried the same mutation, but was symptom free, as most female carriers are.) The older brother was mentally retarded, probably due to periods of dehydration in infancy as a result of NDI. He could not obtain stable employment and had an unsatisfactory social life. The younger brother had stable employment and a normal social life. During a water deprivation test, the older brother still could not concentrateurine, and injections of syntheticvasopressin (DDAVP) did not decrease his urinary output, whereas the younger brother was able to increase the concentration of his urine and did decrease his urinary output after DDAVP.

The R137H mutation has consistently been associated with severe NDI symptoms in people expressing the mutations. The researchers suggest that the milder symptoms of the younger brother could be due either to some modifying circumstances in the younger brother's V2R gene or variants in other genes involved in the urine-concentratingpathway. They also suggest that the consequences of NDI can be mitigated by early diagnosis along with proper treatment and pertinent information, and perhaps this accounted for the different outcomes in the brothers.

X-linked nephrogenic diabetes insipidus

DEFINITION:

A form of diabetes insipidus, inherited as an X-linked trait, caused by failure of the renal tubules to reabsorb water in response to antidiuretic hormone, without disturbance in the renal filtration and solute excretion rates; the condition does not respond to exogenous vasopressin.

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

inherited

DEFINITION:

That which has been acquired by transmission from parent to offspring.

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

mutations

DEFINITION:

1. Changes in form, quality, or some other characteristic.

2. In genetics, permanent transmissible changes in the genetic material, usually in a single gene.

See definitions for individual types of mutations under "mutation."

AVPR2 gene

DEFINITION:

Arginine-vasopressin receptor 2 gene.

encodes

DEFINITION:

Converts (a message, information, etc.) into code.

arginine vasopressin

DEFINITION:

Vasopressin containing arginine, as that from most mammals, including man.

AVP

DEFINITION:

Arginine vasopressin.

receptor

DEFINITION:

1. A molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., membrane receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and nuclear receptors for steroid hormones.

2. A sensory nerve terminal that responds to stimuli of various kinds; classified in various ways including by the type of stimulus and by the location in the body.

V2 receptor - The structure to which the antidiuretic hormone, arginine vasopressin binds.

V2R

DEFINITION:

Vasopressin-2 receptor.

V2R

DEFINITION:

Vasopressin-2 receptor.

mediates

DEFINITION:

Accomplishes indirectly; accomplishes by the aid of an intervening medium.

antidiuretic

DEFINITION:

1. Suppressing the rate of urine formation.

2. An agent that suppresses urine formation.

AVP

DEFINITION:

Arginine vasopressin.

principal cells

DEFINITION:

1. The fundamental cells of an organ, which usually have a specific function.

2. The principal cells are the chief cells, i.e., the most abundant cells of the parathyroid glands, being polygonal epithelial cells with a granular cytoplasm and vesicular nuclei, arranged in plates or cords, and which are rich in glycogen: the clear cells are more numerous and have relatively large nuclei and clear cytoplasm with few granules, while the dark cells are smaller with smaller and darker nuclei and finely granular cytoplasm with many granules. Intermediate forms also exist.

collecting duct

DEFINITION:

See under duct.

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

phenotype

DEFINITION:

1. The entire physical, biochemical, and physiological makeup of an individual as determined both genetically and environmentally, as opposed to genotype. 2. The expression of a single gene or gene pair.

intrafamilial

DEFINITION:

Within a family.

phenotype

DEFINITION:

1. The entire physical, biochemical, and physiological makeup of an individual as determined both genetically and environmentally, as opposed to genotype. 2. The expression of a single gene or gene pair.

variability

DEFINITION:

The state of being variable.

novel

DEFINITION:

Of a new kind, or different from anything seen or known before.

X-linked NDI

DEFINITION:

A form of diabetes insipidus, inherited as an X-linked trait, caused by failure of the renal tubules to reabsorb water in response to antidiuretic hormone, without disturbance in the renal filtration and solute excretion rates; the condition does not respond to exogenous vasopressin.

histidine

DEFINITION:

An essential amino acid, a-amino-1H-imidazole-4-propanoic acid, first found as a decomposition product of the protamine of sturgeon testes (Kossel, 1896); it is obtainable from many proteins by the action of sulfuric acid and water. The decarboxylation of histidine results in the formation of histamine. Symbol His.

arginine

DEFINITION:

An amino acid produced by the hydrolysis or digestion of proteins.

AVPR2

DEFINITION:

Arginine-vasopressin receptor 2 gene.

mutation

DEFINITION:

frameshift mutation - A mutation resulting from an addition or subtraction that is not an exact multiple of 3 base pairs in a coding sequence. From the point of mutation onwards, base triplets (codons) are read out of phase; the reading frame of the gene is changed, and a completely different set of amino acids is made into protein.

loss-of-function mutation - Impairment of the function of a gene caused by mutation.

missense mutation - A mutation that changes a codon so that it codes for a different amino acid.

nonsense mutation - A mutation in which one of the three terminator codons in the mRNA (UAG, amber; UAA, ochre; UGA, umber or opal), used to signal the end of a polypeptide, appears in the middle of a genetic message, causes premature termination of transcription, and releases incomplete, generally nonfunctional polypeptides from the ribosome.

V2R

DEFINITION:

Vasopressin-2 receptor.

adenylate cyclase

DEFINITION:

An enzyme of the lyase class that catalyzes the formation of 3',5'-cyclic AMP from ATP. The enzyme occurs in plasma cell membranes and is activated by certain hormones (epinephrine, vasopressin, glucagon, and corticotropin). The resultant cyclic AMP serves as an important metabolic regulator.

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

urinary osmolality

DEFINITION:

The concentration of osmotically active particles in solution (in this case, urine) expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions: osmotic pressure, boiling point elevation, freezing point depression, and vapor pressure lowering.

plasma osmolality

DEFINITION:

See individual entries for plasma and osmolality .

water deprivation

DEFINITION:

A method for testing the body's ability to concentrate urine when plasma osmolality is artificially increased. See also water deprivation test .

infusion

DEFINITION:

1. The steeping of a substance in water to obtain its medicinal principles.

2. The product of the process of steeping a drug for extraction of its medicinal principles.

3. The therapeutic introduction of a fluid other than blood, as saline solution, into a vein.

NOTE---An infusion flows in by gravity, an injection is forced in by a syringe, an instillation is dropped in, an insufflation is blown in, and an infection slips in unnoticed.

arginine vasopressin

DEFINITION:

Vasopressin containing arginine, as that from most mammals, including man.

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

phenotype

DEFINITION:

1. The entire physical, biochemical, and physiological makeup of an individual as determined both genetically and environmentally, as opposed to genotype. 2. The expression of a single gene or gene pair.

proband

DEFINITION:

An affected person ascertained independently of his relatives in a genetic study. Called also propositus .

clinical phenotype

DEFINITION:

The clinical expression of a single gene or gene pair.

urinary concentrating ability

DEFINITION:

This is the extent to which the kidneys are able to manufacture urine rich in dissolved wastes yet low in water. The ability to form concentrated urine protects the body from hypertonic dehydration. Conversely, the kidney’s ability to produce dilute, or hypotonic, urine defends the body fluids from hypotonic overhydration (Crawford).

water deprivation

DEFINITION:

A method for testing the body's ability to concentrate urine when plasma osmolality is artificially increased. See also water deprivation test .

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

phenotype

DEFINITION:

1. The entire physical, biochemical, and physiological makeup of an individual as determined both genetically and environmentally, as opposed to genotype. 2. The expression of a single gene or gene pair.

genetic

DEFINITION:

1. Relating to or determined by the origin, development, or causal antecedents of something.

2. Of, relating to, or being a gene.

kidney

DEFINITION:

One of a pair of vertebrate organs situated in the body cavity near the spinal column that excrete waste products of metabolism, in man are bean-shaped organs about 4-1/2 inches long lying behind the peritoneum in a mass of fatty tissue, and consist chiefly of nephrons by which urine is secreted, collected, and discharged into a main cavity whence it is conveyed by the ureter to the bladder.

congenital nephrogenic diabetes insipidus

DEFINITION:

A condition involving the kidneys (see nephrogenic diabetes insipidus) which exists at, and usually before, birth. Congenital refers to conditions that are present at birth, regardless of their causation.

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

mutations

DEFINITION:

1. Changes in form, quality, or some other characteristic.

2. In genetics, permanent transmissible changes in the genetic material, usually in a single gene.

See definitions for individual types of mutations under "mutation."

vasopressin-2 receptor

DEFINITION:

The molecular structure within a cell or on the surface to which the antidiuretic hormone, arginine vasopressin, binds.

V2R

DEFINITION:

Vasopressin-2 receptor.

gene

DEFINITION:

A segment of a DNA molecule that contains all the information required for synthesis of a product (polypeptide chain or RNA molecule), including both coding and non-coding sequences. It is the biological unit of heredity, self-reproducing, and transmitted from parent to progeny. Each gene has a specific position (locus) on the chromosome map. From the standpoint of function, genes are conceived of as structural, operator, and regulatory genes.

wild-type gene - The normal allele of a gene, sometimes symbolized by +.

X-linked gene - A gene carried on the X chromosome; the corresponding trait, whether dominant or recessive, is always expressed in males, who have only one X chromosome. X linkage is used sometimes synonymously with sex linkage since no genetic disorders have as yet been associated with genes on the Y chromosome.

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

mutations

DEFINITION:

1. Changes in form, quality, or some other characteristic.

2. In genetics, permanent transmissible changes in the genetic material, usually in a single gene.

See definitions for individual types of mutations under "mutation."

V2R gene

DEFINITION:

Vasopressin-2 receptor gene.

expression

DEFINITION:

1. The aspect or appearance of the face (or surface of a cell) as determined by the physical or emotional state.

2. The act of squeezing or evacuating by pressure; a term used in pharmacy, surgery, and obstetrics.

3. The detectable effect of a gene.

4. A representation of value, relation, or the like (e.g., ratio).

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

voiding

DEFINITION:

A casting out as of waste matter.

dilute urine

DEFINITION:

A less concentrated form of urine.

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

V2R gene

DEFINITION:

Vasopressin-2 receptor gene.

mutation

DEFINITION:

frameshift mutation - A mutation resulting from an addition or subtraction that is not an exact multiple of 3 base pairs in a coding sequence. From the point of mutation onwards, base triplets (codons) are read out of phase; the reading frame of the gene is changed, and a completely different set of amino acids is made into protein.

loss-of-function mutation - Impairment of the function of a gene caused by mutation.

missense mutation - A mutation that changes a codon so that it codes for a different amino acid.

nonsense mutation - A mutation in which one of the three terminator codons in the mRNA (UAG, amber; UAA, ochre; UGA, umber or opal), used to signal the end of a polypeptide, appears in the middle of a genetic message, causes premature termination of transcription, and releases incomplete, generally nonfunctional polypeptides from the ribosome.

mutation

DEFINITION:

frameshift mutation - A mutation resulting from an addition or subtraction that is not an exact multiple of 3 base pairs in a coding sequence. From the point of mutation onwards, base triplets (codons) are read out of phase; the reading frame of the gene is changed, and a completely different set of amino acids is made into protein.

loss-of-function mutation - Impairment of the function of a gene caused by mutation.

missense mutation - A mutation that changes a codon so that it codes for a different amino acid.

nonsense mutation - A mutation in which one of the three terminator codons in the mRNA (UAG, amber; UAA, ochre; UGA, umber or opal), used to signal the end of a polypeptide, appears in the middle of a genetic message, causes premature termination of transcription, and releases incomplete, generally nonfunctional polypeptides from the ribosome.

NDI

DEFINITION:

water deprivation test

DEFINITION:

A test of the body's ability to concentrate urine when plasma osmolality is artificially increased.

concentrate

DEFINITION:

1. To bring to a common center; to gather together at one point.

2. To increase the strength by diminishing the bulk of, as of a liquid; to condense.

3. A drug or other preparation that has been strengthened by the evaporation of its non-active parts.

urine

DEFINITION:

The fluid excreted by the kidneys, passed through the ureters, stored in the bladder, and discharged through the urethra. Urine, in health, has an amber color, a slight acid reaction, a peculiar odor, and a bitter, saline taste.

synthetic

DEFINITION:

Artificial. See also synthesis .

vasopressin

DEFINITION:

1. One of two octapeptide hormones formed by the neuronal cells of the hypothalamic nuclei and stored in the posterior lobe of the pituitary gland (neurohypophysis), the other being oxytocin. It stimulates the contraction of the muscular tissue of the capillaries and arterioles, raising the blood pressure. It promotes contraction of the intestinal musculature and increases peristalsis, and also exerts some contractile influence on the uterus. It also has a specific effect on the epithelial cells of the distal portion of the uriniferous tubule, augmenting resorption of water independently of solutes, resulting in concentration of urine and dilution of blood serum. Its rate of secretion is regulated chiefly by the osmolarity of the plasma.

2. [USP], A pharmaceutical preparation of the same principle, prepared synthetically or obtained from the posterior pituitary of healthy domestic animals used for food by man; used mainly as an antidiuretic in the treatment of acute or chronic diabetes insipidus, administered intramuscularly as a test of hypothalamo-neurohypophysial-renal function in distinguishing central from nephrogenic diabetes insipidus; it may also be used to stimulate smooth muscle tissue, especially to induce vasoconstriction in the presence of hemorrhage. Called also antidiuretic hormone (ADH).

dDAVP

DEFINITION:

Also DDAVP. Trademark for preparation of desmopressin.

urinary output

DEFINITION:

The amount of urine excreted by the kidneys.

concentration

DEFINITION:

1. Increase in strength by evaporation.

2. The ratio of the mass or volume of a solute to the mass or volume of the solution or solvent.

urine

DEFINITION:

The fluid excreted by the kidneys, passed through the ureters, stored in the bladder, and discharged through the urethra. Urine, in health, has an amber color, a slight acid reaction, a peculiar odor, and a bitter, saline taste.

urinary output

DEFINITION:

The amount of urine excreted by the kidneys.

dDAVP

DEFINITION:

Also DDAVP. Trademark for preparation of desmopressin.

mutations

DEFINITION:

1. Changes in form, quality, or some other characteristic.

2. In genetics, permanent transmissible changes in the genetic material, usually in a single gene.

See definitions for individual types of mutations under "mutation."

residue

DEFINITION:

1. A remainder; that which remains after the removal of other substances. 2. In biochemistry, the portion of a molecule that remains after it has lost some of its components, as an amino acid residue, which loses a water molecule when it is joined to another amino acid.

vasopressin-2 receptor

DEFINITION:

The molecular structure within a cell or on the surface to which the antidiuretic hormone, arginine vasopressin, binds.

proteins

DEFINITION:

Any of a group of complex organic compounds which contain carbon, hydrogen, oxygen, nitrogen, and usually sulfur, the characteristic element being nitrogen, and which are widely distributed in plants and animals. Proteins, the principal constituents of the protoplasm of all cells, are of high molecular weight and consist essentially of combinations of a-amino acids in peptide linkages. Twenty different amino acids are commonly found in proteins, and each protein has a unique, genetically defined amino acid sequence which determines its specific shape and function. They serve as enzymes, structural elements, hormones, immunoglobulins, etc., and are involved in oxygen transport, muscle contraction, electron transport, and other activities throughout the body, and in photosynthesis.

binding protein - any of a number of plasma proteins (See below) that bind to hormones of low solubility (chiefly the thyroid and steroid hormones), thus providing a transport system for them; some are specific for particular hormones, while others bind to any sparingly soluble hormones. Called also carrier protein or transport protein (See below).

carrier proteins - A binding protein (See above).

plasma proteins - The hundreds of different proteins present in blood plasma, including carrier proteins (such as albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotensin and bradykinin, and many other types of proteins.

transport protein - binding protein (See above).

cell surface

DEFINITION:

See plasma membrane.

molecular sequence

DEFINITION:

See definition 3 under sequence.

kidney

DEFINITION:

One of a pair of vertebrate organs situated in the body cavity near the spinal column that excrete waste products of metabolism, in man are bean-shaped organs about 4-1/2 inches long lying behind the peritoneum in a mass of fatty tissue, and consist chiefly of nephrons by which urine is secreted, collected, and discharged into a main cavity whence it is conveyed by the ureter to the bladder.

concentrate

DEFINITION:

1. To bring to a common center; to gather together at one point.

2. To increase the strength by diminishing the bulk of, as of a liquid; to condense.

3. A drug or other preparation that has been strengthened by the evaporation of its non-active parts.

urine

DEFINITION:

The fluid excreted by the kidneys, passed through the ureters, stored in the bladder, and discharged through the urethra. Urine, in health, has an amber color, a slight acid reaction, a peculiar odor, and a bitter, saline taste.

NDI

DEFINITION:

Nephrogenic diabetes insipidus.

expressing

DEFINITION:

1. Indicating the flow of genetic information from gene to protein.

2. Regulating the process by which the effects of a gene are manifested.

3. Manifesting a heritable trait in an individual carrying the gene or genes that determine it.

mutations

DEFINITION:

1. Changes in form, quality, or some other characteristic.

2. In genetics, permanent transmissible changes in the genetic material, usually in a single gene.

See definitions for individual types of mutations under "mutation."

V2R gene

DEFINITION:

Vasopressin-2 receptor gene.

genes

DEFINITION:

In the singular: A segment of a DNA molecule that contains all the information required for synthesis of a product (polypeptide chain or RNA molecule), including both coding and non-coding sequences. It is the biological unit of heredity, self-reproducing, and transmitted from parent to progeny. Each gene has a specific position (locus) on the chromosome map. From the standpoint of function, genes are conceived of as structural, operator, and regulatory genes.

wild-type gene - The normal allele of a gene, sometimes symbolized by +.

X-linked gene - A gene carried on the X chromosome; the corresponding trait, whether dominant or recessive, is always expressed in males, who have only one X chromosome. X linkage is used sometimes synonymously with sex linkage since no genetic disorders have as yet been associated with genes on the Y chromosome.

urine

DEFINITION:

The fluid excreted by the kidneys, passed through the ureters, stored in the bladder, and discharged through the urethra. Urine, in health, has an amber color, a slight acid reaction, a peculiar odor, and a bitter, saline taste.

concentrating

DEFINITION:

1. Bringing to a common center; gathering together at one point.

2. Increasing the strength by diminishing the bulk of, as of a liquid; condensing.

3. The strengthening of a drug or other preparation by the evaporation of its non-active parts.

pathway

DEFINITION:

1. A path or course, especially a course followed in the attainment of a specific end. 2. The nerve structures through which an impulse passes between groups of nerve cells or between the central nervous system and an organ or muscle. 3. Metabolic pathway.